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Hyperbranched poly(ethylenimine-co-oxazoline) by thiol–yne chemistry for non-viral gene delivery : investigating the role of polymer architecture
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Cook, Alexander B., Peltier, Raoul, Zhang, Junliang, Gurnani, Pratik, Tanaka, Joji, Burns, James A., Dallmann, Robert, Hartlieb, Matthias and Perrier, Sébastien (2019) Hyperbranched poly(ethylenimine-co-oxazoline) by thiol–yne chemistry for non-viral gene delivery : investigating the role of polymer architecture. Polymer Chemistry, 10 (10). pp. 1202-1212. doi:10.1039/C8PY01648H ISSN 1759-9954.
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Official URL: http://dx.doi.org/10.1039/C8PY01648H
Abstract
Cationic polymers have been widely employed as gene delivery vectors to help circumvent extracellular and intracellular delivery barriers. Among them, polyethylenimine (PEI) is the most commonly used despite its associated high cytotoxicity. PEI is typically obtained by uncontrolled ring opening polymerisation of aziridine, leading to either linear polymer architectures with only secondary amines, or branched architectures containing primary, secondary, and tertiary amines. In contrast, we describe the preparation of hyperbranched poly(ethylenimine-co-oxazoline) that contains only secondary amines, via a fast thiol–yne based one pot reaction. A small library of these compounds with varying PEI contents was then used to study the effect of polymer architecture on pDNA polyplex formation, cytotoxicity, and in vitro transfection studies with plasmid DNA. Hyperbranched poly(ethylenimine-co-oxazoline) was found to have reduced toxicity compared to the commercial standard 25 000 g mol−1 branched PEI (bPEI), with transfection efficiencies only slightly lower than its bPEI counterpart. Obtained results highlight the importance of the polymer architecture on the transfection efficiency of a gene delivery system, which was demonstrated by excluding other parameters such as molecular weight and charge density.
Item Type: | Journal Article | ||||||||||||||||||||||||
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Subjects: | Q Science > QD Chemistry R Medicine > RB Pathology |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Gene therapy, Addition polymerization, Amines | ||||||||||||||||||||||||
Journal or Publication Title: | Polymer Chemistry | ||||||||||||||||||||||||
Publisher: | Royal Society of Chemistry | ||||||||||||||||||||||||
ISSN: | 1759-9954 | ||||||||||||||||||||||||
Official Date: | 29 January 2019 | ||||||||||||||||||||||||
Dates: |
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Volume: | 10 | ||||||||||||||||||||||||
Number: | 10 | ||||||||||||||||||||||||
Page Range: | pp. 1202-1212 | ||||||||||||||||||||||||
DOI: | 10.1039/C8PY01648H | ||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||||||||
Date of first compliant deposit: | 22 February 2019 | ||||||||||||||||||||||||
Date of first compliant Open Access: | 29 January 2020 | ||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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